| Literature References | 1. KETCHUM, K.A., JOINER, W.J., SELLERS, A.J., KACZMAREK, L.K.
AND GOLDSTEIN, S.A.N.
A new family of outwardly rectifying potassium channel proteins with two
pore domains in tandem.
NATURE 376 690-695 (1995).
2. GOLDSTEIN, S.A.N., PRICE, L.A., ROSENTHAL, D.N. AND PAUSCH, M.H.
ORK1, a potassium-selective leak channel with two pore domains cloned from
Drosophila melanogaster by expression in Saccharomyces cerevisiae.
PROC.NATL.ACAD.SCI.U.S.A. 93 13256-13261 (1996).
3. FINK, M. DUPRAT, F., LESAGE, F., REYES, R., ROMEY, G., HEURTEAUX, C.
AND LAZDUNSKI, M.
Cloning, functional expression and brain localization of a novel
unconventional outward rectifier K+ channel.
EMBO J. 15 6854-6862 (1996).
4. LESAGE, F., GUILLEMARE, E., FINK, M., DUPRAT, F., LAZDUNSKI, M.,
ROMEY, G. AND BARHANIN, J.
TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with novel
structure.
EMBO J. 15 1004-1011 (1996).
5. DUPRAT, F., LESAGE, F., FINK, M., REYES, R., HEURTEAUX, C.
AND LAZDUNSKI, M.
TASK, a human background K+ channel to sense external pH variations near
physiological pH.
EMBO J. 16 5464-5471 (1997).
6. FINK, M., LESAGE, F., DUPRAT, F., HEURTEAUX, C., REYES, R., FOSSET, M.
AND LAZDUNSKI, M.
A neuronal two P domain K+ channel stimulated by arachidonic acid and
polyunsaturated fatty acids.
EMBO J. 17 3297-3308 (1998).
|
| Documentation | Potassium (K+) channels play a key role in many cellular functions, in both
excitable and non-excitable tissues. Among the ion channels, they form the
largest family in terms of both structure and function. K+ channel subunits
contain a conserved pore-forming motif, the P-domain, which is considered
to be an essential element of the aqueous K+-selective pore. Shaker-type
and Kir K+ channel subunits both contain a single P-domain, and four such
subunits are thought to associate to form a multimer, together with
associated auxillary (regulatory) subunits. Recently, a new class of K+
channel subunit was cloned, which is clearly distinct from the Shaker and
Kir families; the new class contains not one but two P-domains in each
subunit, and evidence suggests a complete channel may be formed by the
dimerisation of two such subunits.
The first member of this family (TOK1), cloned from S.cerevisiae [1], is
predicted to have eight potential transmembrane (TM) helices. However,
subsequently-cloned two P-domain family members from Drosophila and
mammalian species are predicted to have only four TM segments. They are
usually referred to as TWIK-related channels (Tandem of P-domains in a
Weakly Inward rectifying K+ channel) [2-6]. Functional characterisation of
these channels has revealed a diversity of properties in that they may show
inward or outward rectification, their activity may be modulated in
different directions by protein phosphorylation, and their sensitivity to
changes in intracellular or extracellular pH varies. Despite these
disparate properties, they are all thought to share the same topology of
four TM segments, including two P-domains. That TWIK-related K+ channels
all produce instantaneous and non-inactivating K+ currents, which do not
display a voltage-dependent activation threshold, suggests that they are
background (leak) K+ channels involved in the generation and modulation of
the resting membrane potential in various cell types. Further studies have
revealed that they may be found in many species, including: plants,
invertebrates and mammals.
2POREKCHANEL is a 2-element fingerprint that provides a signature for the
two pore domain K+ channel family. The fingerprint was derived from an
initial alignment of 10 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length - motifs 1 and 2 each
encoding part of one of the K+ channel pore-forming domains. Three
iterations on SPTR37_10f were required to reach convergence, at which point
a true set comprising 51 sequences was identified.
An update on SPTR57.15_40.15f identified a true set of 345 sequences.
|